We propose to develop a novel gravimetric detection element for use in self-contained microelectromechanical systems (MEMS) based biosensors. The detection element consists of a MEMS membrane resonator functionalized with a recognition group (e.g. ligand, receptor, lectin, antibody, oligonucleotide, peptide, nucleic acid). Binding of target analyte to the functionalized resonator increases the mass of the vibrating element, resulting in a measurable decrease in its resonant frequency. Gravimetric detection enables direct determination of adsorbed mass without probe moieties and permits chip-based biosensors to be self-contained as only sample and power need be supplied and provision for signal readout made. The proposed detector should have superior sensitivity to that of existing acoustic-wave gravimetric sensors including macroscopic quartz crystal microbalances and MEMS-based resonant structures including plates, cantilever and films due to its dramatically increased surface area-to-mass ratio, enabling greater amounts of analyte to be bound per unit mass of the resonant element and larger resonant frequency depressions relative to the initial resonant frequency for a given adsorbed mass. The design for this detector is based on a complementary metal-oxide semiconductor (CMOS) MEMS membrane originally developed at Carnegie Mellon as a speaker for hearing aid applications. In the R21 phase we aim to resize, functionalize, instrument and package this membrane for use as a gravimetric detector and to validate its performance. We also aim to develop a quantitative simulation tool that may be used to guide the physical design of the detector in terms of membrane and functionalization properties and solution damping; further this tool will provide quantitative targets by which response and sensitivity performance may be assessed. In the R33 phase we aim to optimize detector performance, guided by our simulation tool, in terms of the shape, size and elasticity of the MEMS membrane, the shape, size and density of the functionalized region of the membrane and the geometry of the fluidic reservoir and to extend this detector concept to multi-analyte applications via arrays of individual detector elements and by poly-functionalizing individual detector elements.